Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An immunohistochemical and morphometric analysis was performed on trephine biopsy specimens in 60 patients with chronic myeloid leukemia (CML) to quantify erythropoiesis and its proliferation capacity and to assess the stainable marrow iron (hemosiderin). For this purpose, an elaborate double-immunostaining technique was applied. This included a monoclonal antibody (PC10) that is directed against proliferating cell nuclear antigen (PCNA), followed by an antibody against glycophorin C (Ret40f), to identify all nucleated erythroid precursor cells. Additionally, morphometric data were derived from immunostaining of megakaryocytes (CD61) and macrophages (PG-M1), including its hemosiderin-laden subpopulation. Finally the determination of argyrophilic (reticulin) fiber density was carried out. In comparison with a control group (15 patients) without any hematologic disorder, in CML patients morphometric evaluation showed a significant reduction in the number of erythroblasts and normoblasts. This feature was associated with a PCNA-labeling index within the normal range and a decreased stainable marrow iron (number of hemosiderin-storaging macrophages). Several parameters were established to exert a predictive value on survival. A worsening of prognosis was associated with a decrease in the number of erythroid precursors (< 460/mm2), a low hemoglobin level (< 10 g/dl), a high megakaryocyte count (> 50 cells/mm2), an increased density of reticulin fibers (> 30 i x 10(2)/mm2) and splenomegaly (> 15 cm below costal margin). Our findings are in keeping with results obtained from in vitro studies of cell proliferation in CML, which is not significantly altered in comparison with the normal bone marrow. Finally, the present data, although derived from a small group of patients, emphasize the impact of histologic variables to be included in one of the major clinical trials on prognosis in CML.
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PMID:Erythropoiesis in CML--immunomorphometric quantification, PCNA-reactivity, and influence on survival. 790 86

To determine parameters of predictive value in CML, a retrospective clinico-pathological study was performed. This included laboratory data and (pretreatment) bone marrow biopsies of 120 patients with a monotherapy by busulfan (BU) and 50 patients with interferon-alpha 2b (IFN) treatment. Median survival in the BU group was 39 months and in the IFN-treated patients 65 months. Morphological features (CD61-positive megakaryocytes, argyrophilic fibres, pseudo-Gaucher cells) were evaluated by morphometry. Additionally, we measured the incidence of apoptosis (in situ end-labelling technique) and the expression of the proliferating cell nuclear antigen (PCNA). The ratio between the proliferative and apoptotic cell fraction was coined leukaemia turnover index (LTI). In order to estimate the impact of clinical and various morphological as well as dynamic features of prognostic significance, a multivariate analysis was carried out using the classification and regression tree approach (CART). Discrimination of single disease parameters revealed that fibrosis remained the most significant variable for survival in both therapeutic groups. Indicators of myeloid metaplasia such as occurrence of erythro-normoblasts and/or splenomegaly were important clinical parameters for prognosis. Inclusion of morphological as well as dynamic disease features in risk classification resulted in a substantial improvement of prognostic efficiency compared to other predictive scores which could be demonstrated by means of ROC-analysis.
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PMID:Impact of clinical and morphological variables in classification and regression tree-based survival (CART) analysis of CML with special emphasis on dynamic features. 945 26

A multicenter, immunohistochemical and morphometric study was performed on diagnostic pretreatment bone marrow biopsies in 614 adult patients with Ph1+ chronic myeloid leukemia (CML) to compare histological features with clinical findings. For identification of megakaryopoiesis we used the monoclonal antibody CD61 and additionally the PAS reaction to determine the subfraction of atypical micromegakaryocytes and precursors. Labelling of erythroid precursors was carried out by a monoclonal antibody directed against glycophorin C. In order to selectively stain macrophages and their activated subset we applied CD68 and the GSA-I lectin. Density of argyrophilic fibers (reticulin plus collagen) was measured following Gomori's silver impregnation method. In accordance with laboratory data morphological variables revealed a comparable amount of congruence in the various groups of CML patients derived from different sources. In about 26% of patients early (reticulin) to advanced (collagen) fibrosis was detectable. Significant correlations were calculated between the extent of myelofibrosis with splenomegaly, anemia and increasing numbers of erythroblasts and myeloblasts in the peripheral blood count. These features were assumed to indicate more advanced stages of the disease process with ensuing transition into myeloid metaplasia and consequently were associated with an unfavorable prognosis. Significant relationships were revealed between the number of CD61+ megakaryocytes and more important, also their precursor fraction with the degree of fibrosis. This result extends previous experimental findings regarding the impact of immature elements of this cell lineage for the generation of myelofibrosis. The significant association of erythroid precursors with the number of mature (resident) macrophages including their activated GSA-I subset may shed some light on their functional involvement in iron turnover and hemoglobin synthesis. A modified histological classification of predominant bone marrow features is introduced. This simplified synthesis staging system (Cologne Classification) is not only associated with certain sets of laboratory data, but also with different survival patterns.
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PMID:Bone marrow features and clinical findings in chronic myeloid leukemia--a comparative, multicenter, immunohistological and morphometric study on 614 patients. 1067 1

The effect of imatinib on myeloproliferative disease in transgenic (Tg) mice expressing the P230 BCR/ABL transcript is unknown. To investigate this issue, we administered imatinib (30 mg/kg per day) orally to P230 BCR/ABL-expressing Tg mice for 30 days. Following imatinib administration, the enlarged spleen was significantly reduced to within the normal size range. Infiltrating megakaryocytes in the long-axis section of the spleen were also significantly reduced. However, the cellularity of the bone marrow was not affected. Fluorescence-activated cell-sorting analysis revealed that infiltrating mature granulocytes in the spleen were reduced in number. The numbers of infiltrating CD34, CD117, CD61, and CD11b populations were also reduced in immature populations of the spleen. Real-time quantitative polymerase chain reaction analysis of messenger RNA revealed a dramatic reduction in the p230 BCR/ABL transcript for CD34, CD117, CD61, and CD11b populations in both bone marrow cells and spleen cells. Western blotting and immunoprecipitation analysis also revealed a marked reduction in P230 BCR/ABL protein expression in both bone marrow cells and spleen cells. Thus, imatinib administration had the intriguing effect of replacing clones with high expression of p230 BCR/ABL complementary DNA with clones with very low expression. These data show that imatinib may still be capable of eliminating and eradicating clones with high p230 BCR/ABL expression and healing the disease phenotype in Tg mice. Pluripotent clones with very low p230 BCR/ABL expression still survive as immature CD34, CD117, CD61, and CD11b populations.
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PMID:Oral administration of imatinib to P230 BCR/ABL-expressing transgenic mice changes clones with high BCR/ABL complementary DNA expression into those with low expression. 1711 62

Imatinib has shown significant clinical and cytogenetic success in the treatment of chronic myeloid leukemia. Although resistance has been observed in a proportion of patients, sudden blastic crisis is a rare event during imatinib therapy. We describe a 24-year-old male patient with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase who developed sudden blastic crisis in the 24th month of imatinib therapy, with loss of complete cytogenetic response. At this time, the patient had splenomegaly, severe anemia, thrombocytopenia, and leukocytosis. Bone marrow aspirate revealed the presence of massive blastic infiltration with myeloid morphology. Flow cytometric analysis of the bone marrow cells showed positivity for CD45, CD34, CD13, CD33, CD19, CD41, CD61, and glycophorin-A. Trephine biopsy specimens showed 100% cellular marrow with diffuse infiltrate by blasts. A reticulin stain of the bone marrow biopsy section demonstrated severe diffuse fibrosis. Cytogenetic analysis by fluorescence in situ hybridization (FISH) revealed that 92% of the cells were positive for the BCR/ABL fusion signal and had increased copy numbers for chromosomes 8, 13, 19, and 21. The patient's prognosis was unfavorable. In conclusion, chronic myeloid leukemia remains complex and includes unanswered questions. The presented case with a rare event during imatinib therapy highlights the need for the continued monitoring of residual disease and the development of strategies to eliminate residual leukemia cells in patients showing a complete cytogenetic response.
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PMID:Sudden blastic crisis and additional chromosomal abnormalities during chronic myeloid leukemia in the imatinib era. 1996 94

Three dogs of different breeds, ages, and genders were presented with pale mucous membranes, depression, anorexia, and splenomegaly. Observed were severe normocytic, nor-mochromic, nonregenerative anemia, thrombocytopenia, and leukopenia. Blood smears contained large, atypical cells with blue vacuolated cytoplasm, cytoplasmic blebs, round to oval central nuclei, and elevated numbers of cytoplasmic fragment resembling macroplatelets. Bi- and multinucleated atypical cells were found mainly in spleen, lymph nodes, and bone marrow. A final diagnosis of acute megakaryoblastic leukemia (AMegL) was made based on morphology and positivity to the megakaryocyte-derived cell-specific markers von Willebrand factor and CD61. In case nos. 1 and 2, no treatment was initiated, and the dogs died on days 4 and 3, respectively. Case no. 3 received supportive therapy with prednisone, and after a brief improvement the dog died spontaneously 35 days after initial presentation. Only 11 cases of AMegL have been reported in dogs, and the specific diagnostic criteria have not been well established. The presence of vacuolization, cytoplasmic blebs, central round nuclei, cytoplasmic fragments, and multinucleated cells in these three cases were considered useful to differentiate AMegL from other hematopoietic neoplasms.
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PMID:Acute megakaryoblastic leukemia in dogs: a report of three cases and review of the literature. 2081 May 53

CD71 is an immunohistochemical marker used in diagnosing acute myeloid leukemia (AML) M6-Er in humans; however, to our knowledge, it has not been reportedly used for immunohistochemistry in veterinary medicine. We evaluated the pathologic features of AML M6-Er in a retrovirus-negative cat and used CD71 to support the diagnosis. A 4-y-old spayed female Scottish Fold cat was presented with lethargy, anorexia, and fever. Whole-blood PCR assay results for pro feline leukemia virus/pro feline immunodeficiency virus and feline vector-borne diseases were negative. Early erythroid precursors were observed in the peripheral blood smear. Fine-needle aspiration of the enlarged spleen and splenic lymph node showed many early erythroid precursors. Bone marrow aspirate smears revealed erythroid hyperplasia with 68.4% erythroid lineage and 3.6% rubriblasts. Dysplastic cells infiltrated other organs. The patient was diagnosed with myelodysplastic syndrome, progressing to the early phase of AML M6-Er. The patient died on day 121 despite multidrug treatments. Postmortem examination revealed neoplastic erythroblasts infiltrating the bone marrow and other organs. Neoplastic cells were immunopositive for CD71 but immunonegative for CD3, CD20, granzyme B, von Willebrand factor, CD61, myeloperoxidase, and Iba-1. Although further studies are necessary for the application of CD71, our results supported the morphologic diagnosis of AML M6-Er.
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PMID:Anti-CD71 antibody immunohistochemistry in the diagnosis of acute myeloid leukemia, subtype acute erythroid leukemia with erythroid dominance (AML M6-Er), in a retrovirus-negative cat. 3322 61